Release Mechanisms of Amorphous Solid Dispersions: Role of Drug-Polymer Phase Separation and Morphology

Formulating poorly soluble molecules as amorphous solid dispersions (ASDs) is an effective strategy to improve drug release. However, drug release rate and extent tend to rapidly diminish with increasing drug loading (DL).
In this work, release profiles of ASDs formulated with ritonavir (RTV) and polyvinylpyrrolidone/vinyl acetate (PVPVA) at different DLs were determined using surface normalized dissolution.
Surface morphologies of partially dissolved ASD compacts were evaluated with confocal fluorescence microscopy.
ASD phase behavior during hydration and release of components were also visualized in real time using a newly developed in situ confocal fluorescence microscopy method.
The domain size and interconnectivity of phase separated drug-rich domains appear to be critical factors impacting drug release from RTV-PVPVPA ASDs.